Trends in Alcohol‐Related Traffic Risk Behaviors Among College Students

Background: Alcohol‐impaired driving is a major public health problem. National studies indicate that about 25% of college students have driven while intoxicated in the past month and an even greater percentage drive after drinking any alcohol and/or ride with an intoxicated driver. The purpose of this investigation was to examine the change in these various alcohol‐related traffic risk behaviors as students progressed through their college experience. Methods: A cohort of 1,253 first‐time first‐year students attending a large, mid‐Atlantic university were interviewed annually for 4 years. Repeated measures analyses were performed using generalized estimating equations to evaluate age‐related changes in prevalence and frequency of each behavior (i.e., ages 19 to 22). Results: At age 19, 17%_wt of students drove while intoxicated, 42%_wt drove after drinking any alcohol, and 38%_wt rode with an intoxicated driver. For all 3 driving behaviors, prevalence and frequency increased significantly at age 21. Males were more likely to engage in these behaviors than females. To understand the possible relationship of these behaviors to changes in drinking patterns, a post hoc analysis was conducted and revealed that while drinking frequency increased every year, frequency of drunkenness was stable for females, but increased for males. Conclusions: Alcohol‐related traffic risk behaviors are quite common among college students and take a significant upturn when students reach the age of 21. Prevention strategies targeted to the college population are needed to prevent serious consequences of these alcohol‐related traffic risk behaviors.     

Analysis of N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine/N1‐acetyl‐5‐methoxy‐kynuramine formation from melatonin in mice

Abstract: The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N¹‐acetyl‐N²‐formyl‐5‐methoxykynuramine (AFMK) and N¹‐acetyl‐5‐methoxy‐kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy‐AMK and glucuronide‐conjugated hydroxy‐AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress.     

Melatonin enhances L‐DOPA therapeutic effects,helps to reduce its dose,and protects dopaminergic neurons in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐induced parkinsonism in mice

L‐3,4‐dihydroxyphenylalanine (L‐DOPA) reduces symptoms of Parkinson's disease (PD), but suffers from serious side effects on long‐term use. Melatonin (10–30 mg/kg, 6 doses at 10 hr intervals) was investigated to potentiate L‐DOPA therapeutic effects in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced parkinsonism in mice. Striatal tyrosine hydroxylase (TH) immunoreactivity, TH, and phosphorylated ser 40 TH (p‐TH) protein levels were assayed on 7th day. Nigral TH‐positive neurons stereology was conducted on serial sections 2.8 mm from bregma rostrally to 3.74 mm caudally. MPTP caused 39% and 58% decrease, respectively, in striatal fibers and TH protein levels, but 2.5‐fold increase in p‐TH levels. About 35% TH neurons were lost between 360 and 600 μm from 940 μm of the entire nigra analyzed, but no neurons were lost between 250 μm rostrally and 220 μm caudally. When L‐DOPA in small doses (5–8 mg/kg) failed to affect MPTP‐induced akinesia or catalepsy, co‐administration of melatonin with L‐DOPA attenuated these behaviors. Melatonin administration significantly attenuated MPTP‐induced loss in striatal TH fibers (82%), TH (62%) and p‐TH protein (100%) levels, and nigral neurons (87–100%). Melatonin failed to attenuate MPTP‐induced striatal dopamine depletion. L‐DOPA administration (5 mg/kg, once 40 min prior to sacrifice, p.o.) in MPTP‐ and melatonin‐treated mice caused significant increase in striatal dopamine (31%), as compared to L‐DOPA and MPTP‐treated mice. This was equivalent to 8 mg/kg L‐DOPA administration in parkinsonian mouse. Therefore, prolonged, effective use of L‐DOPA in PD with lesser side effects could be achieved by treating with 60% lower doses of L‐DOPA along with melatonin.     

Pre‐transplant comorbidity burden and post‐transplant chronic graft‐versus‐host disease

The Haematopoietic Cell Transplantation‐Comorbidity Index (HCT‐CI) was designed as a predictor of non‐relapse mortality after HCT. Chronic graft‐versus‐host disease (GVHD) contributes to mortality after HCT. Here, we investigated whether the HCT‐CI could predict development of chronic GVHD or post‐chronic GVHD mortality. We retrospectively analysed data from 2909 patients treated with allogeneic HCT for malignant and non‐malignant haematological conditions at four institutions. In Cox regression models adjusted for potential confounders, increasing HCT‐CI was not statistically significantly associated with the development of chronic GVHD [hazard ratio (HR) = 1·02, P = 0·34]. Yet, the index was associated with an increased risk of non‐relapse mortality (HR = 1·29, P < 0·0001) as well as overall mortality (HR = 1·25, P < 0·001) following the development of chronic GVHD. The association between HCT‐CI and post‐chronic GVHD mortality was similar regardless of donor type or stem cell source. HCT‐CI scores could be incorporated in the design of clinical trials for treatment of chronic GVHD.